Hepatitis C virus (HCV) is an important health problem with approximately 1% of the world's population infected with the virus. Over 75% of acutely infected individuals eventually progress to a chronic carrier state that can result in cirrhosis, liver failure, and hepatocellular carcinoma. A very small fraction of chronically infected patients naturally clear the HCV and resolve chronic hepatitis. See Alter et al. (1992) N. Engl. J. Med. 327:1899-1905; Resnick and Koff. (1993) Arch. Intem. Med. 153:1672-1677; Seeff (1995) Gastrointest. Dis. 6:20-27; Tong et al. (1995) N. Engl. J. Med. 332:1463-1466.
There is evidence of the existence of HCV-specific neutralizing antibodies during the course of infection with HCV. See Ishii et al. (1998) Hepatology. 28:1117-1120. Further, the appearance of and maintenance of high serum titers of anti-E2 neutralization of binding (NOB) antibodies in the course of chronic HCV infection has been correlated with protection from HCV infection, HCV clearance, and clinical resolution of HCV liver disease. Ishii et al. (1998); Rosa et al. (1996) Proc. Natl. Acad. Sci. USA 93:1759. However, to date, only purified HCV E2 polypeptides truncated at amino acid 715 have been shown to elicit anti-E2 NOB in animal studies. Foumillier et al. (1999) J. Virology 73:7497-75504. Thus, there remains a need for effective methods of eliciting anti-E2 NOB antibody titers.